Cell membranes provide natural resistance to entry of foreign molecules into the cell cytoplasm. As a result, the effectiveness of many cancer treatment drugs, e.g., chemotherapy agents, is somewhat limited due to the inability of the drugs to penetrate the membrane of the targeted cancer cells.
One known solution to this problem is to increase the dosage of the cancer treatment drug in an effort to provide the desired drug quantity to the targeted cells. However, such elevated dosages may often result in damage to healthy host cells proximate the targeted cells. Therefore, a system and method for introducing a cancer treatment drug into target cells while minimizing the effects on healthy host cells would be beneficial.
To address the problems associated with increased dosage, drug delivery techniques using some degree of cellular stimulation are known. For example, U.S. Pat. No. 5,888,530 to Netti et al. describes a method for enhancing drug delivery by creating a transient differential between a target tissue site and a region near the target tissue site. U.S. Pat. No. 5,386,837 to Sterzer describes a non-invasive technique for applying high frequency wave energy (e.g., RF, microwave, infrared, or ultrasonic) to create transient pores in the membranes of targeted cells through which drug molecules may enter.
Another technique known as electroporation has also been used. Electroporation is a process wherein electrical fields are applied across target cells, usually through the application of multiple electrical pulses. These pulses create transient pores through the cell membrane, yet do not result in permanent cell damage. Molecules of chemotherapeutic drugs delivered during the electroporation process may then more easily enter the cell through these temporary pores.
While promising, most clinical applications of electroporation are presently directed to cutaneous diseases such as melanoma, head and neck squamous cell carcinoma, basal cell carcinoma, and adenocarcinoma.
One cancer treatment electroporation technique is described in U.S. Pat. No. 5,468,223 to Mir. The '223 patent describes delivering a drug followed by transcutaneous electric pulses provided via external electrodes.
Another technique is disclosed in U.S. Pat. No. 5,389,069 to Weaver. The '069 patent discloses placing an electrically conductive penetrator into or proximate the target cells and an electrode on the organism surface. A voltage is then applied between the penetrator and the electrode, causing electroporation of the cells in between.
U.S. Pat. No. 5,674,267 to Mir et al. describes a needle array for introduction into the tissue to be treated. The needle array may produce an electrical pulse between each different pair of needles. U.S. Pat. No. 6,233,482 to Hofmann et al. also discloses an apparatus for in vivo electroporation using a needle array having selectable array switching patterns.
U.S. Pat. Nos. 5,547,467 and 5,667,491, both to Pliquett et al., disclose application of medication to the epidermis of an organism after which the epidermis is electroporated. U.S. Pat. No. 5,749,847 to Zewert et al. describes a similar process for delivering a nucleotide into an organism.
U.S. Pat. No. 6,085,115 to Weaver et al. also describes biopotential measurement by electroporation of a tissue surface, e.g., a skin surface.
Accordingly, electroporation devices are known. While effective for their respective intended purposes, the techniques and apparatus described herein above generally require external attachment or external introduction of the electroporation electrodes and completion of a medical procedure for each chemotherapy session.
A summary of the documents described herein above (as well as others) is provided in Table 1 below.
TABLE 1U.S. Pat. No.InventorIssue Date5,468,223MirNov. 21, 19955,386,837SterzerFeb. 7, 19955,389,069WeaverFeb. 14, 19955,547,467Pliquett et al.Aug. 20, 19965,667,491Pliquett et al.Sep. 16, 19975,674,267Mir et al.Oct. 7, 19975,749,847Zewert et al.May 12, 19985,869,326HofmannFeb. 9, 19995,888,530Netti et al.Mar. 30, 19996,085,115Weaver et al.Jul. 4, 20006,233,482Hofmann et al.May 15, 2001
All documents listed in Table 1 above are hereby incorporated by reference herein in their respective entireties. As those of ordinary skill in the art will appreciate readily upon reading the Summary of the Invention, Detailed Description of the Embodiments, and claims set forth below, at least some of the devices and methods disclosed in the documents of Table 1 and others documents incorporated by reference herein may be modified advantageously by using the teachings of the present invention. However, the listing of any such document in Table I, or elsewhere herein, is by no means an indication that such documents are prior art to the present invention.